SUSTIVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUSTIVA (SUSTIVA).
Non-nucleoside reverse transcriptase inhibitor (NNRTI) which binds to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities, causing a conformational change and inhibiting HIV-1 replication.
| Metabolism | Metabolized primarily by cytochrome P450 (CYP) isoenzymes CYP2B6 and CYP3A4/5; it is a moderate inducer of CYP3A4 and a weak inhibitor of CYP2C9 and CYP2C19. |
| Excretion | Fecal (primarily, ~51% as metabolites, ~14% as unchanged drug); renal (~34%, <1% unchanged). |
| Half-life | 42 hours (range 22–72), steady state achieved in ~7–10 days. |
| Protein binding | ~99% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 2.4 L/kg; extensive tissue distribution including CNS (CSF:plasma ratio ~0.01). |
| Bioavailability | Oral: ~42% (capsules) to ~50% (tablets); increased ~50% with high-fat meal. |
| Onset of Action | Oral: 2–4 weeks for maximal virologic response; rapid absorption with peak plasma at 4–5 hours. |
| Duration of Action | 24 hours; sustained suppression with once-daily dosing. |
600 mg orally once daily, preferably at bedtime to minimize central nervous system symptoms; take on an empty stomach (1 hour before or 2 hours after a meal).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; hemodialysis does not significantly affect elimination. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): 600 mg once daily; Moderate hepatic impairment (Child-Pugh B): 400 mg once daily or 200 mg twice daily; Severe hepatic impairment (Child-Pugh C): contraindicated. |
| Pediatric use | For patients ≥3 months and weighing ≥3.5 kg: weight-based dosing capsules or oral solution; 600 mg (tablet) for ≥40 kg; dose formulations vary by weight bands; consult specific guidelines. |
| Geriatric use | No specific dose adjustment required; monitor for CNS symptoms and hepatic function due to age-related changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SUSTIVA (SUSTIVA).
| Breastfeeding | Efavirenz is excreted in human breast milk. The milk-to-plasma ratio is approximately 0.5-1.0. Due to the potential for HIV transmission, adverse effects in the infant, and drug resistance, breastfeeding is not recommended in HIV-infected mothers. If alternative antiretroviral therapy is not available, caution is advised. |
| Teratogenic Risk | FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use in pregnant women despite potential risks. Efavirenz is associated with an increased risk of neural tube defects when administered during the first trimester. Animal studies have shown increased fetal resorptions and malformations. Use only if benefit outweighs risk, and avoid during first trimester if possible. |
■ FDA Black Box Warning
Efavirenz can cause hepatotoxicity, including severe hepatic necrosis and hepatic failure. Discontinue if liver toxicity is suspected. Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C).
| Serious Effects |
Moderate to severe hepatic impairment (Child-Pugh Class B or C), concomitant use with drugs that are highly dependent on CYP3A4 for clearance (e.g., astemizole, terfenadine, ergot alkaloids, midazolam, triazolam, pimozide), and known hypersensitivity to efavirenz or any component of the formulation.
| Precautions | Hepatotoxicity (monitor liver enzymes), psychiatric symptoms (including depression, suicidal ideation, psychosis), severe skin reactions (e.g., Stevens-Johnson syndrome), immune reconstitution syndrome, fat redistribution, hyperlipidemia, decreased bone mineral density, convulsions (use with caution in patients with history of seizures), and potential for drug interactions. |
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| Fetal Monitoring | Monitor maternal liver function tests, lipid profile, and CD4 count. Perform pregnancy testing before initiation. In pregnant women, perform fetal ultrasound during first trimester to detect neural tube defects. Monitor for signs of teratogenicity and neonatal toxicity (e.g., CNS effects, hyperbilirubinemia). Monitor infant for HIV status and adverse effects postnatally. |
| Fertility Effects | Efavirenz does not appear to significantly impair fertility in animal studies. In humans, limited data suggest no major impact on male or female fertility. However, hormonal contraceptives may be less effective due to enzyme induction; use additional barrier methods. |